Investigations in GABAA receptor antibody-associated encephalitis

Objective: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABA(A) receptor (GABA(A)R) encephalitis. Methods: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to alpha 1, beta 3, and gamma 2 subunits of the GABA(A)R were determined using reported techniques. Results: Patients' median age was 40.5 years (interquartile range 48.5 [13.75- 62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical- subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures (p = 0.007) and movement disorders (p = 0.01) and less likely to have a tumor (p 5 0.01). The main epitope targets were in the alpha 1/beta 3 subunits of the GABA(A)R. Conclusions: Anti-GABA(A)R encephalitis is characterized by frequent seizures and distinctive multifocal cortical- subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment.